PMID- 19862817
OWN - NLM
STAT- MEDLINE
DCOM- 20100308
LR  - 20211203
IS  - 0008-543X (Print)
IS  - 0008-543X (Linking)
VI  - 116
IP  - 1
DP  - 2010 Jan 1
TI  - Preliminary characterization of oral lesions associated with inhibitors of 
      mammalian target of rapamycin in cancer patients.
PG  - 210-5
LID - 10.1002/cncr.24696 [doi]
AB  - BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitors may have efficacy as 
      an intervention for advanced malignancies. Oral ulceration (OU), reported as 
      mucositis, has been a dose-limiting toxicity for this new class of agents. An 
      analysis of the appearance, course, and toxicity associations of mTOR 
      inhibitor-associated stomatitis (mIAS) demonstrated that the condition is 
      distinct from conventional mucositis (CM) and more closely resembles aphthous 
      stomatitis. METHODS: Safety data from 78 solid tumor patients enrolled in 2 Phase 
      1, multicenter trials of the mTOR inhibitor deforolimus (AP23573, MK-8669) were 
      evaluated. Adverse events (AEs) based on National Cancer Institute Common 
      Toxicity Criteria for National Cancer Institute Common Terminology Criteria for 
      Adverse Events (version 3.0) criteria were coded, consolidated, and stratified 
      according to the presence or absence and duration of concordant OU. The relation 
      between OU and other AEs was analyzed. RESULTS: Treatment-emergent AEs were 
      reported in 91% of 78 study participants. OUs were reported in 66%, appeared 
      within 5 days of deforolimus administration, and were discrete, ovoid, 
      superficial, well demarcated, and surrounded by an erythematous halo. Their 
      clinical appearance and distribution were similar to that of aphthous stomatitis 
      but inconsistent with CM. Patients with OU were more likely to have nonspecific 
      rashes and acneiform dermatitis but not gastrointestinal AEs. CONCLUSIONS: OU 
      associated with mTOR inhibitor therapy differed from CM. Lesions more closely 
      resembled those of aphthous stomatitis. The lack of other gastrointestinal 
      involvement but the presence of a higher incidence of concomitant cutaneous AEs 
      provided additional evidence to suggest a distinction between mIAS and CM. 
      Treatment strategies for aphthous stomatitis may be a rational approach for the 
      prevention and control of mIAS.
CI  - Copyright 2010 American Cancer Society.
FAU - Sonis, Stephen
AU  - Sonis S
AD  - Division of Oral Medicine and Dentistry, Brigham and Women's Hospital and 
      Dana-Farber Cancer Institute, Boston, MA02115, USA. ssonis@partners.org
FAU - Treister, Nathaniel
AU  - Treister N
FAU - Chawla, Sant
AU  - Chawla S
FAU - Demetri, George
AU  - Demetri G
FAU - Haluska, Frank
AU  - Haluska F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer
JT  - Cancer
JID - 0374236
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 48Z35KB15K (ridaforolimus)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antineoplastic Agents/*adverse effects
MH  - Clinical Trials, Phase I as Topic
MH  - Female
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/*antagonists & inhibitors
MH  - Male
MH  - Middle Aged
MH  - Mucositis/*chemically induced
MH  - Neoplasms/drug therapy
MH  - Protein Serine-Threonine Kinases/*antagonists & inhibitors
MH  - Sirolimus/adverse effects/*analogs & derivatives
MH  - Stomatitis/chemically induced
MH  - TOR Serine-Threonine Kinases
EDAT- 2009/10/29 06:00
MHDA- 2010/03/10 06:00
CRDT- 2009/10/29 06:00
PHST- 2009/10/29 06:00 [entrez]
PHST- 2009/10/29 06:00 [pubmed]
PHST- 2010/03/10 06:00 [medline]
AID - 10.1002/cncr.24696 [doi]
PST - ppublish
SO  - Cancer. 2010 Jan 1;116(1):210-5. doi: 10.1002/cncr.24696.